Skip to main content
Erschienen in: Pediatric Radiology 10/2017

04.05.2017 | Original Article

Pediatric imaging in DICER1 syndrome

verfasst von: Marta Tijerin Bueno, Claudia Martínez-Ríos, Alejandro De la Puente Gregorio, Rayan A. Ahyad, Anita Villani, Harriet Druker, Kalene van Engelen, Bailey Gallinger, Laura Aronoff, Ronald Grant, David Malkin, Mary-Louise C. Greer

Erschienen in: Pediatric Radiology | Ausgabe 10/2017

Einloggen, um Zugang zu erhalten

Abstract

Background

DICER1 syndrome, arising from a mutation in the DICER1 gene mapped to chromosome 14q32, is associated with an increased risk of a range of benign and malignant neoplasms.

Objective

To determine the spectrum of abnormalities and imaging characteristics in patients with DICER1 syndrome at a tertiary pediatric hospital.

Materials and methods

This retrospective analysis evaluated imaging in patients ≤18 years with DICER1 germline variants between January 2004 and July 2016. An imaging database search including keywords pleuropulmonary blastoma, cystic nephroma, pineoblastoma, embryonal rhabdomyosarcoma, ovarian sex cord-stromal tumor, ovarian Sertoli-Leydig cell tumor and DICER1 syndrome, was cross-referenced against the institutional Cancer Genetics Program database, excluding patients with negative/unknown DICER1 gene testing.

Results

Sixteen patients were included (12 females; mean age at presentation: 4.2 years, range: 14 days to 17 years), with surveillance imaging encompassing the following modalities: chest X-ray and CT; abdominal, pelvic and neck US; and brain and whole-body MRI. Malignant lesions (68.8% of patients) included pleuropulmonary blastoma (5), pineoblastoma (3), ovarian Sertoli-Leydig cell tumor (1), embryonal rhabdomyosarcoma (1) and renal sarcoma (1); benign lesions (37.5% of patients) included thyroid cysts (2), thyroid nodules (2), cystic nephroma (2), renal cysts (1) and pineal cyst (1). A common lesional appearance observed across modalities and organs was defined as the “cracked windshield” sign.

Conclusion

The spectrum of DICER1-related tumors and the young age at presentation suggest early surveillance of at-risk patients is critical, while minimizing exposure to ionizing radiation.
Literatur
1.
Zurück zum Zitat Slade I, Bacchelli C, Davies H et al (2011) DICER1 syndrome: clarifying the diagnosis, clinical features and management implications of a pleiotropic tumour predisposition syndrome. J Med Genet 48:273–278CrossRefPubMed Slade I, Bacchelli C, Davies H et al (2011) DICER1 syndrome: clarifying the diagnosis, clinical features and management implications of a pleiotropic tumour predisposition syndrome. J Med Genet 48:273–278CrossRefPubMed
2.
Zurück zum Zitat Online Mendelian Inheritance in Man. National Center for Biotechnology Information website. http://www.ncbi.nlm.-nih.gov/omim. (http://www.omim.org/entry/606241). Accessed 27 May 2016 Online Mendelian Inheritance in Man. National Center for Biotechnology Information website. http://​www.​ncbi.​nlm.​-nih.​gov/​omim.​ (http://​www.​omim.​org/​entry/​606241). Accessed 27 May 2016
3.
Zurück zum Zitat Foulkes WD, Priest JR, Duchaine TF (2014) DICER1: mutations, microRNAs and mechanisms. Nat Rev Cancer 14:662–672CrossRefPubMed Foulkes WD, Priest JR, Duchaine TF (2014) DICER1: mutations, microRNAs and mechanisms. Nat Rev Cancer 14:662–672CrossRefPubMed
5.
Zurück zum Zitat Online Mendelian Inheritance in Man. National Center for Biotechnology Information website. http://www.ncbi.nlm.-nih.gov/omim. (http://www.omim.org/entry/601200). Accessed 27 May 2016 Online Mendelian Inheritance in Man. National Center for Biotechnology Information website. http://​www.​ncbi.​nlm.​-nih.​gov/​omim.​ (http://​www.​omim.​org/​entry/​601200). Accessed 27 May 2016
6.
Zurück zum Zitat Priest JR, Watterson J, Strong L et al (1996) Pleuropulmonary blastoma: a marker for familial disease. J Pediatr 128:220–224CrossRefPubMed Priest JR, Watterson J, Strong L et al (1996) Pleuropulmonary blastoma: a marker for familial disease. J Pediatr 128:220–224CrossRefPubMed
8.
Zurück zum Zitat de Kock L, Druker H, Weber E et al (2015) Ovarian embryonal rhabdomyosarcoma is a rare manifestation of the DICER1 syndrome. Hum Pathol 46:917–922CrossRefPubMed de Kock L, Druker H, Weber E et al (2015) Ovarian embryonal rhabdomyosarcoma is a rare manifestation of the DICER1 syndrome. Hum Pathol 46:917–922CrossRefPubMed
9.
Zurück zum Zitat Wu MK, Goudie C, Druker H et al (2016) Evolution of renal cysts to anaplastic sarcoma of kidney in a child with DICER1 syndrome. Pediatr Blood Cancer 63:1272–1275CrossRefPubMed Wu MK, Goudie C, Druker H et al (2016) Evolution of renal cysts to anaplastic sarcoma of kidney in a child with DICER1 syndrome. Pediatr Blood Cancer 63:1272–1275CrossRefPubMed
10.
Zurück zum Zitat Wu MK, Cotter MB, Pears J (2016) Tumor progression in DICER1-mutated cystic nephroma - witnessing the genesis of anaplastic sarcoma of the kidney. Hum Pathol 53:114–120CrossRefPubMed Wu MK, Cotter MB, Pears J (2016) Tumor progression in DICER1-mutated cystic nephroma - witnessing the genesis of anaplastic sarcoma of the kidney. Hum Pathol 53:114–120CrossRefPubMed
11.
Zurück zum Zitat Kuhlen M, Hönscheid A, Schemme J et al (2016) Hodgkin lymphoma as a novel presentation of familial DICER1 syndrome. Eur J Pediatr 175:593–597CrossRefPubMed Kuhlen M, Hönscheid A, Schemme J et al (2016) Hodgkin lymphoma as a novel presentation of familial DICER1 syndrome. Eur J Pediatr 175:593–597CrossRefPubMed
12.
Zurück zum Zitat Foulkes WD, Bahubeshi A, Hamel N et al (2011) Extending the phenotypes associated with DICER1 mutations. Hum Mutat 32:1381–1384CrossRefPubMed Foulkes WD, Bahubeshi A, Hamel N et al (2011) Extending the phenotypes associated with DICER1 mutations. Hum Mutat 32:1381–1384CrossRefPubMed
14.
Zurück zum Zitat Messinger YH, Stewart DR, Priest JR et al (2015) Pleuropulmonary blastoma: a report on 350 central pathology-confirmed pleuropulmonary blastoma cases by the international Pleuropulmonary Blastoma registry. Cancer 121:276–285CrossRefPubMed Messinger YH, Stewart DR, Priest JR et al (2015) Pleuropulmonary blastoma: a report on 350 central pathology-confirmed pleuropulmonary blastoma cases by the international Pleuropulmonary Blastoma registry. Cancer 121:276–285CrossRefPubMed
15.
Zurück zum Zitat Schultz KA, Harris A, Williams GM et al (2014) Judicious DICER1 testing and surveillance imaging facilitates early diagnosis and cure of pleuropulmonary blastoma. Pediatr Blood Cancer 61:1695–1697CrossRefPubMedPubMedCentral Schultz KA, Harris A, Williams GM et al (2014) Judicious DICER1 testing and surveillance imaging facilitates early diagnosis and cure of pleuropulmonary blastoma. Pediatr Blood Cancer 61:1695–1697CrossRefPubMedPubMedCentral
16.
Zurück zum Zitat Bahubeshi A, Bal N, Rio Frio T et al (2010) Germline DICER1 mutations and familial cystic nephroma. J Med Genet 47:863–866CrossRefPubMed Bahubeshi A, Bal N, Rio Frio T et al (2010) Germline DICER1 mutations and familial cystic nephroma. J Med Genet 47:863–866CrossRefPubMed
17.
Zurück zum Zitat Cajaiba MM, Khanna G, Smith EA et al (2016) Pediatric cystic nephromas: distinctive features and frequent DICER1 mutations. Hum Pathol 48:81–87CrossRefPubMed Cajaiba MM, Khanna G, Smith EA et al (2016) Pediatric cystic nephromas: distinctive features and frequent DICER1 mutations. Hum Pathol 48:81–87CrossRefPubMed
18.
Zurück zum Zitat Faure A, Atkinson J, Bouty A et al (2016) DICER1 pleuropulmonary blastoma familial tumour predisposition syndrome: what the paediatric urologist needs to know. J Pediatr Urol 12:5–10CrossRefPubMed Faure A, Atkinson J, Bouty A et al (2016) DICER1 pleuropulmonary blastoma familial tumour predisposition syndrome: what the paediatric urologist needs to know. J Pediatr Urol 12:5–10CrossRefPubMed
19.
Zurück zum Zitat Schultz KA, Harris A, Messinger Y et al (2016) Ovarian tumors related to intronic mutations in DICER1: a report from the international ovarian and testicular stromal tumor registry. Familial Cancer 15:105–110CrossRefPubMedPubMedCentral Schultz KA, Harris A, Messinger Y et al (2016) Ovarian tumors related to intronic mutations in DICER1: a report from the international ovarian and testicular stromal tumor registry. Familial Cancer 15:105–110CrossRefPubMedPubMedCentral
20.
Zurück zum Zitat Heravi-Moussavi A, Anglesio MS, Cheng SW et al (2012) Recurrent somatic DICER1 mutations in nonepithelial ovarian cancers. N Engl J Med 366:234–242CrossRefPubMed Heravi-Moussavi A, Anglesio MS, Cheng SW et al (2012) Recurrent somatic DICER1 mutations in nonepithelial ovarian cancers. N Engl J Med 366:234–242CrossRefPubMed
21.
Zurück zum Zitat Conlon N, Schultheis AM, Piscuoglio S et al (2015) A survey of DICER1 hotspot mutations in ovarian and testicular sex cord-stromal tumors. Mod Pathol 28:1603–1612CrossRefPubMedPubMedCentral Conlon N, Schultheis AM, Piscuoglio S et al (2015) A survey of DICER1 hotspot mutations in ovarian and testicular sex cord-stromal tumors. Mod Pathol 28:1603–1612CrossRefPubMedPubMedCentral
22.
Zurück zum Zitat Oue T, Inoue M, Kubota A et al (2008) Pediatric thyroid cancer arising after treatment for pleuropulmonary blastoma. Pediatr Blood Cancer 50:901–902CrossRefPubMed Oue T, Inoue M, Kubota A et al (2008) Pediatric thyroid cancer arising after treatment for pleuropulmonary blastoma. Pediatr Blood Cancer 50:901–902CrossRefPubMed
23.
Zurück zum Zitat de Kock L, Sabbaghian N, Soglio DB (2014) Exploring the association between DICER1 mutations and differentiated thyroid carcinoma. J Clin Endocrinol Metab 99:E1072–E1077CrossRefPubMed de Kock L, Sabbaghian N, Soglio DB (2014) Exploring the association between DICER1 mutations and differentiated thyroid carcinoma. J Clin Endocrinol Metab 99:E1072–E1077CrossRefPubMed
24.
Zurück zum Zitat Rutter MM, Jha P, Schultz KA et al (2016) DICER1 mutations and differentiated thyroid carcinoma: evidence of a direct association. J Clin Endocrinol Metab 101:1–5CrossRefPubMed Rutter MM, Jha P, Schultz KA et al (2016) DICER1 mutations and differentiated thyroid carcinoma: evidence of a direct association. J Clin Endocrinol Metab 101:1–5CrossRefPubMed
25.
26.
Zurück zum Zitat Richards S, Aziz N, Bale S et al (2015) Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 17:405–424 Richards S, Aziz N, Bale S et al (2015) Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 17:405–424
27.
Zurück zum Zitat Kleinerman RA (2009) Radiation-sensitive genetically susceptible pediatric sub-populations. Pediatr Radiol 39(Suppl 1):S27–S31CrossRefPubMed Kleinerman RA (2009) Radiation-sensitive genetically susceptible pediatric sub-populations. Pediatr Radiol 39(Suppl 1):S27–S31CrossRefPubMed
28.
Zurück zum Zitat Brenner DJ, Shuryak I, Einstein AJ (2011) Impact of reduced patient life expectancy on potential cancer risks from radiologic imaging. Radiology 261:193–198CrossRefPubMed Brenner DJ, Shuryak I, Einstein AJ (2011) Impact of reduced patient life expectancy on potential cancer risks from radiologic imaging. Radiology 261:193–198CrossRefPubMed
29.
Zurück zum Zitat Brady Z, Ramanauskas F, Cain TM et al (2012) Assessment of paediatric CT dose indicators for the purpose of optimisation. Br J Radiol 85:1488–1498CrossRefPubMedPubMedCentral Brady Z, Ramanauskas F, Cain TM et al (2012) Assessment of paediatric CT dose indicators for the purpose of optimisation. Br J Radiol 85:1488–1498CrossRefPubMedPubMedCentral
30.
Zurück zum Zitat Doros LA, Rossi CT, Yang J et al (2014) DICER1 mutations in childhood cystic nephroma and its relationship to DICER1-renal sarcoma. Mod Pathol 27:1267–1280CrossRefPubMedPubMedCentral Doros LA, Rossi CT, Yang J et al (2014) DICER1 mutations in childhood cystic nephroma and its relationship to DICER1-renal sarcoma. Mod Pathol 27:1267–1280CrossRefPubMedPubMedCentral
31.
Zurück zum Zitat Oliveira C, Himidan S, Pastor AC et al (2011) Discriminating preoperative features of pleuropulmonary blastomas (PPB) from congenital cystic adenomatoid malformations (CCAM): a retrospective, age-matched study. Eur J Pediatr Surg 21:2–7CrossRefPubMed Oliveira C, Himidan S, Pastor AC et al (2011) Discriminating preoperative features of pleuropulmonary blastomas (PPB) from congenital cystic adenomatoid malformations (CCAM): a retrospective, age-matched study. Eur J Pediatr Surg 21:2–7CrossRefPubMed
32.
Zurück zum Zitat Kousari YM, Khanna G, Hill DA et al (2014) Case 211: pleuropulmonary blastoma in association with cystic nephroma-DICER1 syndrome. Radiology 273:622–625CrossRefPubMed Kousari YM, Khanna G, Hill DA et al (2014) Case 211: pleuropulmonary blastoma in association with cystic nephroma-DICER1 syndrome. Radiology 273:622–625CrossRefPubMed
33.
Zurück zum Zitat Chong AL, Grant RM, Ahmed BA et al (2010) Imaging in pediatric patients: time to think again about surveillance. Pediatr Blood Cancer 55:407–413CrossRefPubMed Chong AL, Grant RM, Ahmed BA et al (2010) Imaging in pediatric patients: time to think again about surveillance. Pediatr Blood Cancer 55:407–413CrossRefPubMed
34.
Zurück zum Zitat Anupindi SA, Bedoya MA, Lindell RB et al (2015) Diagnostic performance of whole-body MRI as a tool for cancer screening in children with genetic cancer-predisposing conditions. AJR Am J Roentgenol 205:400–408CrossRefPubMed Anupindi SA, Bedoya MA, Lindell RB et al (2015) Diagnostic performance of whole-body MRI as a tool for cancer screening in children with genetic cancer-predisposing conditions. AJR Am J Roentgenol 205:400–408CrossRefPubMed
Metadaten
Titel
Pediatric imaging in DICER1 syndrome
verfasst von
Marta Tijerin Bueno
Claudia Martínez-Ríos
Alejandro De la Puente Gregorio
Rayan A. Ahyad
Anita Villani
Harriet Druker
Kalene van Engelen
Bailey Gallinger
Laura Aronoff
Ronald Grant
David Malkin
Mary-Louise C. Greer
Publikationsdatum
04.05.2017
Verlag
Springer Berlin Heidelberg
Erschienen in
Pediatric Radiology / Ausgabe 10/2017
Print ISSN: 0301-0449
Elektronische ISSN: 1432-1998
DOI
https://doi.org/10.1007/s00247-017-3875-0

Weitere Artikel der Ausgabe 10/2017

Pediatric Radiology 10/2017 Zur Ausgabe

Hermes

Hermes

Minisymposium: Imaging of childhood tuberculosis

Extrapulmonary involvement in pediatric tuberculosis

Minisymposium: Imaging of childhood tuberculosis

Revisiting and redefining the standards in tuberculosis imaging

Update Radiologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.